Synergy between transforming growth factor-beta and tumor necrosis
factor-alpha in the induction of monocytic differentiation of human
leukemic cell lines
F De Benedetti, LA Falk, LR Ellingsworth, FW Ruscetti and CR Faltynek
Laboratory of Biochemical Physiology, Program Resources, Inc., National
Cancer Institute, Frederick, MD 21701.
We examined the effect of transforming growth factor-beta (TGF-beta) alone
and in combinations with other factors on the growth and differentiation of
the human promyelocytic cell line HL60 and the human monoblastic cell line
U937. Treatment with TGF-beta alone did not significantly affect growth or
differentiation of HL60 cells, while it significantly inhibited
proliferation and induced monocytic differentiation of a small percentage
of U937 cells. Combinations of TGF-beta and tumor necrosis factor-alpha
(TNF-alpha) acted in synergy to inhibit cell proliferation and to induce
monocytic differentiation of both HL60 and U937 cells. In contrast, no
synergy was observed when HL60 cells were treated with TGF-beta in various
combinations with interferon-alpha (IFN-alpha), interferon-gamma
(IFN-gamma), and retinoic acid. Examination of TNF-alpha receptor
expression on HL60 and U937 cells showed that these cell lines expressed
comparable levels of high-affinity TNF-alpha binding sites. Treatment of
HL60 and U937 cells with TGF-beta did not induce significant changes in
TNF-alpha receptor expression in either cell line. In contrast, HL60 cells
expressed much lower levels of TGF-beta receptors than did U937 cells.
Treatment of both HL60 and U937 cells with TNF-alpha induced a
dose-dependent increase in expression of TGF-beta receptors, suggesting
that the synergy between TNF-alpha and TGF-beta may result, at least in
part, from upregulation of TGF-beta receptor expression by TNF-alpha.
Volume 75,
Issue 3,
pp. 626-632,
02/01/1990
Copyright © 1990 by The American Society of Hematology
